This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The 90-kDa ribosomal S6 kinase 2 (RSK2) is important serine-threonine kinase broadly expressed in response to various growth factors. RSK pathway is a key regulator of cancer cell proliferation. In humans, RSK2 gene mutations are manifested in Coffin-Lowry syndrome characterized by severe psychomotor retardation. Elucidating the molecular structure of full length RSK2 is essential for understanding its activation mechanism. RSK2 belongs to the family of unusual serine-threonine kinases that contain two distinct kinase domains connected by a linker region. The mitogen- and stress-reguated kinase 1 (MSK1) is close homologue to RSK2 with the same domain organization. The crystal structure of both proteins, RSK2 and MSK1 are not available. We plan to determine crystals structure of full length RSK2 and MSK1. We will need to perform anomalous diffraction experiments at Se-edge energy for Se/Met protein in order to get the data for Se/Met full length MSK1, which is already purified.